Cell mediated immunity (CMI) has not been extensively studied in sickle cell disease (SCD). In this study, an assessment of lymphocyte blastogenic responses was done in 62 SCD patients (62 steady state and 25 in crisis with or without documented infection), along with 30 normal controls in good health and 10 with various infections. The mitogen phytohemagglutinin (PHA) and two antigens (Candida albicans and Tetanus Toxoid) were used as stimuli. An evaluation of these results by stimulation index revealed 53/62 (86%) of SCD steady state patients, 30/30 (100%) of healthy controls and 7/10 (70%) of normal control patients with infection positively responded to all three stimuli. Conversely, only 5/25 (20%) of SCD crisis state patients had totally normal blastogenic responses. Analysis of the data from SCD crisis patients revealed 14/20 (70%) with abnormally depressed proliferation to PHA, 11/20 (55%) to Candida and 6/20 (30%) to Tetanus. When comparisons were made by mean counts per minute, the most striking finding was the PHA response in the SCD crisis state. In this group the mean counts per minute were significantly less than the three other groups by statistical analysis. This data suggests that the crisis state, especially when associated with infection, profoundly effects blastogenic responses to PHA and to a lesser degree in vitro antigenic stimulation. The normal group with infection showed similar diminished blastogenesis to antigen, but no effect on mitogen response.