A cohort of patients with sickle cell disease, consisting of children, adolescents, and adults, who reported experiencing three or more episodes of vaso-occlusive pain the preceding year, were enrolled in a prospective two-period treatment protocol. Following a 4-month conventional treatment baseline phase, a supplemental cognitive-behavioral pain management program that centered on self-hypnosis was implemented over the next 18 months. Frequency of self-hypnosis group straining sessions began at once per week for the first 6 months, became biweekly for the next 6 months, and finally occurred once every third week for the remaining 6 months. Results indicate that the self-hypnosis intervention was associated with a significant reduction in pain days. Both the proportion of "bad sleep" nights and the use of pain medications also decreased significantly during the self-hypnosis treatment phase. However, participants continued to report disturbed sleep and to require medications on those days during which they did experience pain. Findings further suggest that the overall reduction in pain frequency was due to the elimination of less severe episodes of pain. Non-specific factors may have contributed to the efficacy of treatment. Nevertheless, the program clearly demonstrates that an adjunctive behavioral treatment for sickle cell pain, involving patient self-management and regular contact with a medical self-hypnosis team, can be beneficial in reducing recurrent, unpredictable episodes of pain in a patient population for whom few safe, cost-effective medical alternatives exist.