Influence of chlorpromazine (CPZ) on the production of influenza virus was followed in chick embryo cell (CEC) monolayers. CPZ--which binds specifically to calmodulin (CaM)--inhibited in concentration of 20-100 mumol/l the activity of CaM-stimulated 3', 5'-c'AMP phosphodiesterase (PDE). When administered together with the virus, CPZ in concentrations of 20-50 mumol/l reduced virus yields by 2-3 log PFU. Addition of CPZ 15 min before or 1 hr after influenza virus adsorption had no effect. The inhibitory action of CPZ was reversed by purified CaM. The adsorption of influenza virus to CEC or to erythrocytes was not affected. The participation of CaM on the mechanism of influenza virus penetration is discussed.