In vivo exposure of female B6C3F1 mice to gallium arsenide (GaAs) was evaluated for its effect on the in vitro IgM antibody-forming cell (AFC) response. In vivo exposure to a single intratracheal dose of GaAs (2.5-200 mg/kg) resulted in a dose-dependent decrease in the in vitro IgM AFC response to the T-dependent antigen sheep red blood cells (SRBC) with a 97% decrease at 200 mg/kg when compared to vehicle controls. The response to the T-independent antigen DNP-Ficoll was significantly reduced at 100 and 200 mg/kg. Spleen cellularity decreased in a dose-related manner with a 54% decrease at 200 mg/kg. Enumeration of splenic subpopulations following GaAs (200 mg/kg) indicated a 58, 61, and 30% decrease in the total number of Thy 1.2 (T cells), Ig (B cells), and F4/80 (macrophages) positive cells, respectively, with no alterations in the percentages of these cells. Mitogenic responsiveness of splenocytes from GaAs-exposed mice was unaltered. To identify the splenic cell populations targeted by GaAs, the AFC response to SRBC was evaluated following cell separation/reconstitution of splenocytes from GaAs- (200 mg/kg, 24-hr exposure) and vehicle-exposed mice. Results demonstrated AFC suppression was due to functional alterations in both adherent (AD; macrophages) and nonadherent, (both T and B lymphocytes) cell populations. Further investigation focused on alterations in the AD population. Separation/reconstitution experiments demonstrated AFC suppression to SRBC was dependent on the concentration of macrophages from GaAs-exposed mice. This macrophage-mediated suppression of the in vitro AFC response could not be attributed to the presence of suppressor macrophages or release of prostaglandins.