Sodium lauryl sulfate, a model substance in testing skin irritability was examined with regard to its effects on DNA synthesis and fine structure of human thymocytes incubated in vitro. At 5 h, incorporation of 3H-thymidine into DNA was inhibited with a discernable effect at 3 × 10––4 M in serum-free medium and at 6 × 10––4 Min medium to containing 15% serum. Under the former conditions, the effect on DNA synthesis was accompanied by disintegration of the cells as observed electron-microscopically. In contrast, no clear effects on cell morphology were seen in the latter case, in spite of a strongly depressed replicative activity. After 48 h of culture in medium containing 15% serum, there was a marked decrease in cell number due to spontaneous cell death and, consequently, a low rate of DNA synthesis. Sodium lauryl sulfate suppressed the incorporation of 3H-thymidine into DNA at 1.2 × 10––3 M. No clear alterations in cell morphology were observed at 3 × 10––4 M, whereas signs of irreversible cell damage, including pyknotic nuclei, were seen at 6 × 10––4 Mand complete disruption of most cells occurred at 1.2 × 10––3 M. The results show that sodium lauryl sulfate inhibits DNA synthesis in human thymocytes and that there is a partial discrepancy between this inhibition and the adverse effects on the structural organization of the cell. It is proposed that the irritant effect of sodium lauryl sulfate in vivo is due to the breaking up of lymphoid or other cells and a consequent release of material that gives rise to an inflammatory response.