The MDR1 gene product P-glycoprotein (P-gp), a transmembrane efflux pump, is expressed in many normal tissues including subpopulations of normal peripheral blood. To test the potential impact of cigarette smoke and/or a variety of lipophilic industrial solvents present in paint and varnish, P-gp expression in unsorted peripheral blood cells of 51 healthy volunteers was measured by means of immunocytochemistry and daunorubicin uptake studies. 10 of these volunteers were heavy smokers and 10 were working as painters or sprayers, and consequently in regular and intense contact with industrial solvents. Cigarette smoke had no impact with regard to increased P-gp expression and function. However, extensive contact with industrial solvents of lipophilic origin was shown to cause a significant increase in the level of P-gp expression (P < 0.001), thus providing new evidence for the broad substrate specificity of the P-gp pump.