The possibilities of trypanocidal drug synergy have been examined in vitro and in vivo using a monomorphic laboratory strain of Trypanosoma rhodesiense. Twenty-seven different drug pair combinations were chosen from among 12 representative trypanocides on the basis of surmized or reported synergy, evidence of collateral sensitivity in resistant strains, and known differences in modes of action or in field use. In vitro synergy test were made with a transfer plate technique which allows direct isobol determination by microtest tray superimposition. All pairs showing synergy in vitro were tested further in mice. Statistically significant synergy was shown only by suramin and tryparsamide, suramin and Puromycin, and suramin and Berenil. Although six other pairs, of which three contained suramin, showed higher than addictive cure rates, these rates fell short of statistical significance.