Summary:In this study, the comparative effects of half, normal and double clinical doses of artesunate; artesunate/sulfadoxine/pyrimethamine; artesunate/amodiaquine and their combinants (sulfadoxine/pyrimethamine and amodiaquine) on the semen parameters-total sperm count, motility, morphology, debris and premature/primordial cell count of the male guinea-pig were investigated. The agents caused significant (p<0.05) decreases in total sperm count and sperm motility, with increases in abnormal sperm cells (morphology), debris and premature sperm cells. The effects were maximal at the subclinical doses and synergistic in the ACTs, compared to those of the individual partner agents. Artesunate, amodiaquine and artesunate/amodiaquine caused 54, 28 and 84% decreases in total sperm count, with 13, 31 and 64% decreases in sperm motility respectively. Conversely, the above drugs increased baseline morphology by 70, 30 and 264% respectively. Similar synergistic responses were obtained with artesunate/sufadoxine/pyrimethamine. These results may be explained in terms of the oxidative effects of these agents, through generation of free radicals, resulting in pathological damage to testicular structure/function.