C57BL/6J bgJ/bgJ (beige) mice are less sensitive than other strains to the analgesic effects of morphine, although they have normal numbers of mu receptors. In the present study, beige mice and their normal littermates (beige+) were treated in vivo with morphine or the opioid antagonist, naltrexone and their primary in vitro antibody responses were assessed. Morphine treatment caused splenic atrophy and suppressed the primary in vitro antibody response in beige and beige+ mice. However, these effects were not blocked by naltrexone co-treatment. In these mouse strains, naltrexone decreased spleen size and antibody responses by itself, which may mask its ability to antagonize morphine. In beige mice, placebo pellet implantation suppressed the primary in vitro antibody response. Morphine did not cause a further suppression of the antibody response in beige mice compared to placebo. Because of this anomalous response to placebo treatment, the immunosuppressive effects of morphine on the antibody response/10(7) cells can not be attributed to a specific drug effect in this strain. However, when antibody responses were expressed on a per spleen basis, the overall capacity to respond to antigenic challenge was suppressed by morphine treatment.