The hypothesis was tested that the magainin peptides, known to compromise bacterial and mitochondrial energetics, are highly active against spermatozoa. A mixture of magainin A and PGLa (1:1) caused a 50% reduction in motility of hamster spermatozoa at 4-mu-g/ml total peptide concentration. All motility was lost at 8-mu-g/ml. At this concentration. respiratory control was released and respiration in the presence of uncoupler was inhibited. Uptake of the lipophilic cation tetraphenyl phosphonium was largely abolished by addition of magainin A and PGLa at this concentration, indicative of a decrease in the mitochondrial membrane potential. Magainin A and PGLa showed synergism with respect to release of respiratory control.