The mitochondrial enzyme cytochrome-c oxidase (COX) is composed of multiple subunits encoded within both the nuclear and mitochondrial genomes. Isofemale lines of the intertidal copepod Tigriopus californicus showed significant variation in COX activity (measured by a standard spectrophotometric method) both within and between populations. This interline variation was expressed under common culture conditions and is evidence of a genetic component to COX enzymatic activity variation. Because the catalytic core of COX (subunits I, II and III) is encoded by mitochondrial DNA, which is inherited maternally in T. californicus, we hypothesized that variation in COX activity may show maternal inheritance. This hypothesis was evaluated by determining COX activity among F-1 progeny of reciprocal crosses between isofemale lines. Results failed to support the hypothesis; COX activity did not show a pattern of maternal inheritance. Rather, the data suggest that genetic regulation of interline variation in COX activity is complex and involves nuclear genes. In general, F-1 offspring tended to have higher COX activities than either parent, whereas F-2 offspring had enzyme activities similar to or lower than the F-1, suggesting that strong nuclear-nuclear or nuclear-mitochondrial interactions affect COX function.