The effects of thymosin alpha 1 (T alpha 1) and thymopentin (TP5) on the cocaine-induced impairment of the primary antibody response to sheep red blood cells (SRBC) was studied. The administration of cocaine from day -4 to the day of immunization (day 0) induced a significant impairment of the response to the T-dependent antigen SRBC, as evaluated on day 5 post-immunization by the Splenocyte-Induced SRBC Hemolysis (SIH) assay. The analysis of the responses to immunogen elicited from each single mouse indicated that, under the experimental conditions used, cocaine acted by exerting more an "all or nothing" effect rather than by modulating the strength of the immune response. Both T alpha 1 and TP5, injected into mice during cocaine administration and for 4 days after, induced a significant recovery of the response to SRBC. Our experiments did not show any great differences in the overall efficacy of the two drugs, although they showed quite a different dose-response effect. The results of the present investigation demonstrated the capability of TP5 and T alpha 1 to reverse the cocaine-induced impairment of the response to SRBC and suggested that the effect of the two peptides may be related to their immunomodulating activities on T-cell functions.