The effects of anatomical site and occlusion on the percutaneous absorption and residue pattern of total 14C were investigated following topical application of 2,6-[ring-14C]parathion onto four skin sites (300 μg/10 μCi; 40 μg/cm2) in weanling swine using occluded and nonoccluded dosing systems. The excretion profile was examined after iv administration. After dosing onto the abdomen, buttocks, back, and shoulder (N = 4/site), total urinary and fecal excretion (%dose) by 168 hr were, for the occluded system, 43.94 ± 2.24, 48.47 ± 7.85, 48.82 ± 4.49, and 29.28 ± 5.70%, and for the nonoccluded system, 7.47 ± 2.16, 15.60 ± 3.71, 25.00 ± 8.75, and 17.41 ± 1.76%, respectively. After iv dosing 98.44 ± 2.83% of the applied dose was excreted primarily via urine. The total recoveries for different sites ranged from 90.09 ± 7.10 to 94.62 ± 1.98% in the occluded system, 77.84 ± 5.75 to 88.18 ± 3.34% in the nonoccluded system, and 99.03 ± 2.89% in the iv experiments. Time of maximal excretion rate was determined in the occluded system as abdomen (7.9 ± 3.6 hr) < buttocks (9.4 ± 2.6 hr) < shoulder (10.5 ± 3.8 hr) < back (13.3 ± 7.7 hr), but in the nonoccluded system as buttocks (11.9 ± 3.6 hr) < shoulder (12.6 ± 4.1 hr) < back (14.3 ± 6.4 hr) < abdomen (16.9 ± 7.1 hr). The percutaneous absorption from the shoulder was much lower than that from the other three sites under occluded conditions. However, if nonoccluded dosing was employed, absorption from the abdomen became the lowest, with shoulder and buttocks being similar, and the back the highest. Occlusion conceals the site difference and enhances both the extent and the rate of parathion percutaneous absorption in vivo. 14C residue pattern in tissues and dosing materials was site and dosing method dependent, all of which are factors which must be considered when assessing the risk of exposure to topically applied compounds.