The effect of polyploidy on the early development of human embryos is unknown. This study compares the early development of 90 polyploid and 275 diploid human embryos conceived in vitro. Between May 1983 and January 1986, 3081 oocytes were recovered during 631 cycles of laparoscopy for in vitro fertilization (4.9 oocytes/cycle); 1924 oocytes (62.4%) fertilized. There were 90 oocytes with more than two pronuclei (4.7% of fertilized oocytes), identified in 72 cycles (11.4% of cycles). In these cycles, the proportion of diploid oocytes (n = 275) that cleaved (cleavage rate) (92.7%) was significantly greater than the proportion of polyploid oocytes (n = 90) that cleaved (65.5%) (P less than 0.001). The cleavage rate for all diploid oocytes (n = 1834) was 90.4%. There was no significant difference in the stage of development (number of blastomeres; mean +/- standard deviation [SD]) on the day of embryo transfer between diploid (4.3 +/- 2.1) and polyploid (4.1 +/- 2.1) embryos that cleaved, but a plot of the frequency distribution of cleavage stages revealed that significantly more polyploid than diploid embryos had an uneven number of blastomeres at that time (33% versus 8%, respectively; P less than 0.001). Polyploidy confers an immediate developmental disadvantage; one third of polyploid embryos fail to cleave, and those that do divide demonstrate more asynchronous divisions.