The in-vitro and in-vivo effects of cigarette smoke were studied in human peripheral blood lymphocytes by applying a method for the capping of beta 2-microglobulin- or phytohaemagglutinin (PHA)-stimulated lymphocyte transformation (measured as (3H)thymidine incorporation) involving the transglutaminase pseudosubstrate monodansylthiacadaverine (MDTC), whose presence resulted in significantly reduced capping and (3H)thymidine incorporation in a concentration-dependent manner. The addition of dimethyl sulphoxide-soluble particles from cigarette smoke to lymphocytes in vitro significantly reduced the capping ability and the PHA-induced (3H)thymidine incorporation. Whereas no significant change in MDTC-dependent capping inhibition was seen in lymphocytes from smokers after 10 d abstinence from smoking. there was a marked decrease in (3H)thymidine incorporation in lymphocytes from smokers after smoking three cigarettes following 10 h abstinence. The tentative conclusion is that exposure to cigarette smoke, or smoke extract, impairs MDTC-dependent capping inhibition and PHA-stimulated lymphocyte transformation by transglutaminase inhibition.