Prediction of exposure and toxic potential of pesticides such as malathion are routinely based upon acute exposure and single-dose percutaneous absorption determination. What has become obvious with pesticide exposure such as the malathion spraying for the medfly is that chronic daily exposure is the more relevant situation. Our objective was to determine the percutaneous absorption of chronically applied malathion in man and to compare chronic absorption to single-dose absorption. The experimental design was to first topically apply [14C]malathion to human male volunteers. This procedure was followed by repeated administration of nonradioactive malathion to the same site of application (ventral forearm). [14C]Malathion was reapplied (Day 8) when urinary excretion of radioactivity from the first application reached minimum detectable levels. The first [14C]malathion absorption was compared to the second [14C]malathion application. The percutaneous absorption from the first [14C]malathion application was 4.48 +/- 1.3% (SD) of the applied dose. The absorption from the second [14C]malathion administration was 3.53 +/- 1.0%, a value not significantly (p greater than 0.05) different from the first application. Therefore, for malathion the single-dose application data are relevant for predicting the toxic potential for longer-term exposure.