There is limited data on cytokine production in sickle cell disease (SCD). In this study, both alpha (Poly IC-induced) and gamma (PHA-induced) interferon (IFN) were measured in 62 SCD steady state patients, and 21 in the crisis state associated with infections. Comparable normal controls (30 healthy and 14 with infections) were assessed in a similar manner. Gamma IFN production in both SCD groups, steady state (35 +/- 6 U/ml) and crisis state (24 +/- 11 U/ml) was significantly diminished when compared to the normal healthy controls (65 +/- 14 U/ml) with P less than .005. Both SCD groups were also less than normals with infections (56 +/- 23 U/ml) with P less than .005. On closer analysis of individual titers, 15/62 (24%) in the steady state, 11/21 (52%) of SCD patients with infection and 2/14 (14%) of normals with infection, showed impaired gamma IFN when compared to normals without infection (range 27-2187 U/ml). Alpha IFN production in the SCD groups; steady state (512 +/- 113 U/ml) and SCD crisis with infection (559 +/- 110 U/ml) was virtually equivalent to normals (524 +/- 170 U/ml) and normals with infection (509 +/- 116 U/ml). Analysis of individual titers, in contrast to gamma IFN, also showed no significant differences. These results indicate that a significant percentage of SCD patients in both the steady state and infectious state associated with crisis, have impaired gamma IFN production. In view of the known immunomodulatory functions of gamma IFN, this apparent defect may be another factor to explain the increased frequency and severity of infections in SCD.