Populations of the supra-littoral marine copepod Tigriopus californicus are known to be highly divergent and to exhibit a pattern of hybrid breakdown when crossed under laboratory conditions. This dissertation examines the genetic mechanisms involved in hybrid breakdown in T. californicus, particularly those involving integration of the nuclear and mitochondrial genomes. In Chapter I, I summarize some of the relevant literature concerning the importance of hybrid breakdown to evolutionary biology, the integration of nuclear and cytoplasmic components in mitochondria, and the use of T. californicus as a model system. Chapter II reports on the results of an experiment mapping interpopulation hybrid breakdown in T. californicus to the mitochondrial genome. Using a simple backcrossing scheme, this work determines that virtually the entire effect of hybrid breakdown is explained by mitochondrial genotype in hybrids. While an extension of the work examining mitochondrial biochemical capacity yielded a similar result, the results further indicated that the cause of hybrid breakdown in T. californicus likely involved more complex incompatibilities. Chapter III demonstrates that cytonuclear hybrid incompatibilities can manifest themselves in the biochemical performance of mitochondria. Activities of the primary enzyme complexes involved in cellular energy generation were measured in hybrids, as was the overall mitochondrial energy production capacity. Mitochondrial ATP production rate was reduced in hybrids, but only those enzyme complexes requiring the interaction of nuclear and mitochondrial gene products were similarly reduced. This study suggests that failure to integrate nuclear and mitochondrial gene products in hybrids may decrease their capacity to generate cellular energy. Chapter IV examines the impact of hybridization on the nuclear and mitochondrial transcriptional regulatory networks, specifically with regard to genes involved in cellular energy generation. Mitochondrial RNA polymerase genotype is found to have a profound impact on the transcriptional pattern of T. californicus interpopulation hybrids such that particular combinations of mitochondrial RNA polymerase and mitochondrial DNA have a diminished ability to upregulate mitochondrial genes under hypoosmotic stress. The data indicate that the mitochondrial regulatory network may be maintained by compensatory mechanisms in some populations.