A series of 1-alkyl-2-(substituted-amino)-5-hydroxy-4-methylnaphtho[1,2-d]thiazoles having in vitro trypanocidal activity is described. Several caused complete lysis of Trypanosoma brucei organisms within 30 min at 10(-5) M. The presence of a hydrophobic substituent on the 2-amino group was associated with high antitrypanosomal activity. Some analogues unsubstituted at the 1-position, a known class of compounds, were also active. None of the derivatives significantly prolonged the survival of T. brucei infected mice. Inhibition of activity in vitro by bovine serum albumin was observed. Because of the structural novelty of these agents in comparison with known trypanocides, their mechanism of action warrants further investigation.