In the bloodstream of its mammalian host, the African trypanosome Trypanosoma brucei undergoes a life cycle stage differentiation from a long, slender form to a short, stumpy form. This involves three known major events: exit from a proliferative cell cycle, morphological change and mitochondrial biogenesis. Previously, models have been proposed accounting for these events (Matthews and Gull 1994a). Refinement of, and discrimination between, these models has been hindered by a lack of stage–regulated antigens useful as markers at the single–cell level. We have now evaluated a variety of cytological markers and applied them to investigate the coordination of phenotypic differentiation and cell cycle arrest. Our studies have focused on the differential expression of the mitochondrial enzyme dihydrolipoamide dehydrogenase relative to the differentiation–division of bloodstream trypanosomes. The results implicate a temporal order of events: commitment, division, phenotypic differentiation.