Significantly more mouse zygotes developed to blastocysts in culture in a medium formulated on the composition of human tubal fluid (HTF) than in modified Tyrode's medium (T6). In a randomized 2 X 2 factorial trial of human in vitro fertilization that compared the two media and culture under oil versus culture in loosely capped tubes, significantly more clinical pregnancies (30% of 60 transfers) were obtained with HTF medium than with T6 medium (11% of 53 transfers). Decreasing the K+ content of HTF medium to that present in T6 medium significantly decreased the number of mouse zygotes that developed in culture. Modifying Ca++ levels had no effect. It is therefore likely that the higher K+ content in HTF medium is primarily responsible for the superiority of HTF medium over T6 medium, but other differences in the composition of the two media could contribute to the results observed.