The effect of administration of lead acetate (10 mM in the drinking water) for 8 weeks on the in vivo sheep red blood cell (SRBC) specific plaque-forming cell (PFC) responses of inbred A, BALB/c, C57Bl/6, DBA/1, SJL, and NZW/NZB F1 mice and outbred CFW mice was examined to determine if lead was immunomodulatory in a genetically related manner. Lead did not suppress the SRBC-specific PFC/10(6) splenocytes or PFC/spleen response in any mouse strain when compared to the responses of strain-matched control mice. In addition, 10 mM lead-treated BALB/c mice manifested augmented PFC/10(6) splenocytes (17%; p less than .05) but unchanged PFC/spleen responses. Correspondingly, serum concentrations of SRBC-specific antibody (measured by radioimmunoassay) and serum immunoglobulin G, M, or A isotypes were also unchanged by lead acetate treatment in all tested mouse strains. There were no observable lead-related histopathological changes or deposition of immune complexes or antibasement membrane antibody in the kidneys of treated mice. Further, splenocytes from lead-treated, SRBC-immunized mice cultured with T-independent antigens (TNP-LPS, TNP-Ficoll) or with a T-dependent antigen (SRBC) exhibited direct and indirect specific PFC responses that were unchanged from those of control mice. The H-2K/D haplotypes of the outbred CFW mice were determined by microcytotoxicity to include r, q, u, and s. These results suggest that lead acetate (10 mM) administered po for 8 weeks does not suppress the primary direct humoral immune response to SRBC in inbred and outbred mice of several H-2 haplotypes (k/d; d; b; q; d,z; s; r; and u).