Mutations at the period (per) locus (1:1.3; 3B1-2) in Drosophila melanogaster lengthen (perL), shorten (pers), or abolish (per0) overt circadian rhythmicity. Deuterium oxide lengthens the free-running circadian period. We tested the effects of deuterium on three mutants of the per gene (pers, perL, and per0) and wild-type Drosophila melanogaster (per+) to assess interactions. With increasing concentrations of deuterium, the free-running circadian period of locomotor activity rhythms increased. The dose-response was linear in all genotypes tested. With increasing dosages of deuterium, circadian rhythms became weaker as evidenced by the signal-to-noise ratio (SNR). Genotype and deuterium changed circadian period length independently and additively, showing no interaction. SNRs for all genotypes converged on a low level as deuterium concentration increased. Deuterium increased life span, except at high concentrations (40 and 50%).