Knowlton's cactus is one of the rarest cacti in the U.S. It is only known to occre on a small hill in San Juan County, New Mexico. The population was severely impacted when many plants were removed under the mistaken perception that the area was going to be flooded by a newly constructed dam. In May 1985, researchers with the USDI FWS collected 250 stem cuttings from multi-stem plants, grew them in greenhouse conditions, and planted them in three protected sites. Populations slowly dwindled at Nav No.1 from 150 plants introduced 1986 to 69 in 1996, to 20 plants in 2006. BLM No. 1 population declined from 149 in 1991 to 80 in 2000, to 48 in 2008. At Nav No. 2, 102 plants introduced in 1995 declined to 68 in 2000, and 15 in 2006. Researchers last monitored Nav No. 1 & 2 in 2006. The reintroduction sites all had reproductive plants in all years. The first seedling was found in 2002 at Nav No. 1, sixteen years after the introduction was begun. As of 2008, only 6 new cacti have been detected as new recruits in all locations. The clones persisted well for many years, however predation by rabbits and rodents, drought and season of transplantation affected survival. Seed predation is high. 288 seeds planted in 1987 in 3 locations and 3 planting depths had 8 1-3yr old seedlings detected by 1992. By 1997, 18 plants emerged; in 2006 3 remained as adult cacti. Monitoring stopped in 2007. In 1994 another seed trial was initiated with control, brushed, and cultivated treatments: 250 seeds planted at depth of 5mm into each of 3 replications. Twelve seedlings germinated by June 1994. Each year following some seedlings survived and new seedlings emerged. By 2006 104 seedlings grew in all treatment plots combined. Because 2001, 2 seedlings had reached reproductive maturity, new seedlings noted in 2004, 2005, 2006, and 2007 may have been F1s rather than the original seed cohort.

Two reintroduction sites were selected in 1985 nearby the main population in San Juan County, New Mexico. Transplant survival and flowering at these sites have been good, but natural recruitment has been slow. Seeding trials have not resulted in new recruitment (Sivinski and McDonald).

Known from only one viable population in New Mexico's San Juan County. Extensive searches of nearby potential habitat in New Mexico and adjacent Colorado have failed to locate additional natural populations. This species was nearly driven to extinction by cactus collectors within two decades of its discovery; starting from an estimated population size of more than 100,000 plants in 1958, the population was reduced to less than 100 plants by 1978. Although the population was 14,000 in 1994, from 1994 to 2008, a gradual, continuous decline has been documented, likely in response to drought. An increase in rabbit or rodent predation in conjunction with depressed seed production and germination has also been observed. Collection of this species has been greatly reduced but still, some illegal theft is likely occurring.