New phenothiazine derivatives and 4 related lead structures have been studied for their antifilarial and trypanocidal properties. Regarding phenothiazine derivatives, the nitrile group at the 3 position on the phenothiazine ring had a strong in vitro antifilarial effect against Molinema dessetae infective larvae. Among the 4 new lead structures, compound 4 or naphtho(2',3': 4,5) thiazolo(3,2-a)benzimidazole-7,12-dione was the most antifilarial, with IC50 of 8 microM at day 8. These results justify further studies in vivo. A slight effect was observed against the trypanosomes maintained in vitro since minimum inhibitory concentrations of active compounds were 50 microM after a 24-h incubation period. Nevertheless, no trypanocidal activity was observed in vivo after a 100 mg kg-1 treatment and the compound 3 or dibenzo(b,f)(1,4)thiazine-11-amine was lethal at this dose. These new lead structures have now to be optimised using pharmaco-modulations.