The mutagenic activity of the 5-halogen derivatives of deoxyuridine (FUdR, BUdR and IUdR), cytosine arabinoside (CA), 6-azauridine (AzUR) and 6-azacytidine (AzCR) were tested on the male germ line of Drosophila. All compounds were inactive as regards the induction of point mutations (sex-linked recessive lethals and visibles). They were also virtually ineffective in the induction of viable chromosome rearrangements; the highest yield of X-chromosome fragments occurred with IUdR, but only reached a rate of 1 per 10 4 treated gametes. The only mutations induced at an appreciable rate by the tested nucleosides were the small chromosome deletions resulting in the Minute phenotype. Maximal activity in this respect was of the order of 5 mutations per 10 3 treated sperm and was obtained at an injected concentration of 2·0 × 10 −2 M; further increase in dose did not raise the mutation rate. Mutagenic activity was roughly the same for compounds that could enter DNA (BUdR, IUdR and CA) as with those which were not expected to do so (FUdR, AzUR and AzCR). Activity was higher on cells that could undergo nucleoprotein synthesis and chromosome replication (spermatocytes and spermatogonia) than on stages that were inert in this respect (spermatids and sperm). The damage induced consisted of chromosome deletions involving more than one band of the salivary gland chromosome, suggesting the elimination of several DNA molecules. The chromosome breaks leading to the deletions extended across both chromatids, since the resulting Minutes were almost exclusively complete (non-mosaic). The distribution of the Minutes among the chromosomes was somewhat more preferential for the IVth chromosome with the tested compounds, except CA. Consideration was given to the possible genetic hazards to man involved in the chemotherapeutic use of IUdR, AzUR and AzCR. Attention was drawn to the fact that long term genetic hazards were mainly caused by the rise in point-mutations, which persisted for many generations in the human gene pool. Such hazards would not occur with the nucleosides since they were virtually inactive as regards the induction of intragenic changes. Nevertheless, the small chromosome deletions which these agents produced, were expected to result in short term genetic damage in the treated patients and their offspring.