Two established antithyroid drugs, 6-propyl-2-thiouracil and 6-methyl-2-thiouracil, as well as S-methylthiouracil, are shown to be competitive inhibitors of nitric oxide synthase (NOS) (K-1 values ranging from 14 to 60 muM), with moderate selectivity for the neuronal isoform, Other thioureylene and thioamide-containing heterocyclic systems proved virtually ineffective as NOS inhibitors, Besides offering novel useful leads for inhibitor design as well as to probe the active site of neuronal NOS, the results of this study may have interesting implications in relation to the antithyroid activity of thiouracils and their possible neurological effects.