Passive cutaneous anaphylaxis (PCA) was produced in the rat with mouse IgE-rich antiserum. The effect of drugs on the PCA-induced skin histamine decrease and leakage of protein-bound dye was studied. Salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c.) and cromoglycate (10 mg/kg i.v.) significantly inhibited the skin histamine decrease. A combination of salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c.) and aminophylline (25 mg/kg i.v. or 75 mg/kg s.c.) had an additive or greater than additive effect on the histamine decrease. Salbutamol (1.0 mg/kg s.c.) inhibited the dye leakage markedly, and aminophylline (75 mg/kg s.c.) slightly. These results indicate that the decrease in the skin histamine content is useful as an index of the in vivo inhibitory effect of antiallergic drugs on the antigen-induced histamine release.</p