The effects of pentachlorophenol (PCP) on selected parameters reflecting immunocompetence of female B6C3F1 mice were measured following subchronic exposure (14 d) and direct exposure in culture. Daily exposure was by gastric intubation of 10, 30, or 100 mg/kg of technical‐grade PCP (PCP‐T), or 100 mg/kg of EC‐7, a PCP preparation purified to reduce contamination (PCP‐P), or 100 mg/kg of the vehicle, corn oil. There were no effects on the antibody responses of spleen‐cell suspensions from either PCP‐T‐ or PCP‐P‐treated mice stimulated with antigen in culture. In contrast, when mice were immunized during the exposure to PCP‐T, there was a dose‐related suppression of the IgM antibody response to sheep red blood cells (SRBC) measured on both d 4 (peak day) and d 5. There was no change in the antibody response of mice exposed to PCP‐P. The differential activity was not observed following direct addition, since both PCP‐T and PCP‐P suppressed the in vitro antibody response by spleen‐cell suspensions from untreated mice. The suppression was associated with a decrease in cell viability, indicating that both preparations were directly cytotoxic. These results indicate that the in vitro antibody assay will be of limited value in determining the mechanism of immunosuppression by PCP. The lack of effect on the antibody response by splenocytes from PCP‐T‐treated mice indicates that the dysfunction is not due to a direct suppression of the capabilities of immunocompetent cells.