Phenacetin (1), acetaminophen (2), acetanilide (3), 4-aminophenol (4), and aniline (5) were tested in S.J.L. Swiss mice for their mutagenic and analgesic activities. The S-analogues of 1 and 2, 4-mercaptoacetanilide (6) and 4-ethylthioacetanilide (7), respectively, were synthesized and tested in the same way to define if both activities could be separated by molecular modification. All the compounds tested exhibited analgesic activity with ED50 values ranging from 12.6 to 158.5 mg/kg. The compounds could be arranged in a decreasing order of analgesic activity as follows: 3 greater than 4 congruent to 5 congruent to 6 greater than 1 congruent to 7 greater than 2. All the compounds, except 6, were positive mutagens in the micronucleus test (statistically significant). The order of relative mutagenic potencies was 1 congruent to 7 greater than 4 greater than 2 congruent to 3 congruent to 5. A narrow dose-response curve relationship was found for 5 and its metabolite 4, the relative mutagenic potencies of which suggest ring hydroxylation as the major pathway of biotoxification. No parallelism was found between analgesic and mutagenic activities, so they could be separated by pharmacomodulation: 6 was more effective as an analgesic in the acetic acid test than 2, and no mutagenic activity was found at the doses assayed.