The aim of this study was to characterize in greater detail the effects of anti-(rat adipocyte plasma membrane) antisera (A/S 83 and A/S 164) that had previously been shown to cause large reductions in total body fat. Both antisera produced lymphocytic infiltration of adipose tissue and reduction of adipocyte numbers seven days after treatment as well as a reduction in food intake and body weight on the first day of treatment. In addition A/S 164 produced a sedative effect for 2-4 h after treatment and induced gross abnormalities of the liver after seven days. Antibody-mediated complement activation was shown to be a critical requirement for all of these effects since animals treated with cobra venom factor (CVF) to deplete serum complement levels showed none of the described effects. Further evidence in support of a role for complement was the large decrease in serum complement levels 12 h after antiserum treatment. The effects of A/S 164 on liver morphology could be successfully dissociated from those on adipose tissue by adsorption of the antiserum with liver membranes. The adsorbed antiserum, which retained in vitro reactivity with adipose tissue but not with liver, induced a significant reduction in adipose tissue mass in vivo whilst the effect on liver morphology was almost completely abolished. Serum free fatty acid and triglyceride levels increased 6-24 h after treatment but then returned to normal, suggesting a very transient release of adipose tissue triglycerides. These results indicate that complement activation is a common pathway for all of the effects produced.(ABSTRACT TRUNCATED AT 250 WORDS)