The sperm motility stimulants 2-deoxyadenosine (DOA) and pentoxifylline (PTF), used to improve the success of insemination and sperm micro-injection for low motility sperm samples, were studied for their effects on the developmental capacity of mouse and human oocytes. When human oocytes were micro-injected with spermatozoa in 3 mM DOA 80% of them became blocked at the 1-cell pronuclear stage. However, when spermatozoa in 3 mM PTF were used for micro-injection or when spermatozoa were washed to remove DOA before micro-injection only a few oocytes (9-10%) were blocked. Pregnancies occurred in five of 14 patients into whom cleaving embryos from all three treatments had been transferred, indicating that once cleavage was initiated, development of embryos occurred at expected rates. Exposure of mouse oocytes to DOA for a short period during insemination (4-6 h) or a longer period during the pronuclear cell cycle (18-20 h) significantly reduced cleavage beyond the 2-cell stage, resulting in a dramatic reduction in blastocyst formation. PTF did not significantly reduce mouse embryo development. Similar results were obtained for oocytes inseminated in vitro or micro-injected with a spermatozoon into the perivitelline space. Neither DOA nor PTF increased fertilization of mouse oocytes. PTF reduced fertilization, particularly in cumulus-enclosed oocytes and oocytes micro-injected with spermatozoa in PTF. We conclude that DOA is a potent inhibitor of embryo development and oocytes should not be exposed to DOA. Exposure of oocytes to PTF had little effect on their subsequent development but treatment of cauda epididymal mouse spermatozoa can reduce their fertilizing capacity.