Human serum activated with zymosan generates a factor (C5a [a fragment of the 5th complement component]) that releases histamine from autologous basophils. It was previously shown that this mechanism for C5a-induced release differs from Ig[immunoglobulin]E-mediated reactions. The effect of several pharmacologic agents known to alter IgE-mediated release was studied to determine whether they have a similar action on serum-induced release. Deuterium oxide (D2O), which enhances allergic release, inhibited in a concentration-dependent fashion the serum-induced reaction at incubation temperatures of 25 and 32.degree. C. The colchicine-induced inhibition was not reversed by D2O. Cytochalasin B, which gives a variable enhancement of IgE-mediated release, had a marked enhancing effect on the serum-induced reaction in all subjects tested. The following agents known to inhibit the IgE-mediated reaction also inhibited serum-induced release at 25.degree. C: colchicine, dibutyryl cyclic AMP, aminophylline, isoproterenol, cholera toxin, chlorphenesin, diethylcarbamazine and 2-deoxy-D-glucose. The serum-induced release is probably modulated by intracellular cyclic AMP, requires energy, and is enhanced by the disruption of microfilaments. The lack of an effect by D2O would suggest that microtubular stabilization is not required. IgE- and C5a-mediated reactions probably diverge at a late stage in the histamine release pathway.