One time i.p. injections of 5 -20 mg Pregnenolone-16alpha-carbonitrile (PCN) effects the mitotic activity of rat liver cells during a time period of 24 hours to be 20 times higher than the normal mitotic rate. This, however, does not result in an measurable increase of cell numbers and cell volumes. Furthermore, total liver DNA, RNA, protein and dry-weight remain unchanged. The injection of 7 times 10 mg PCN also results in the elevation of the mitotic rate. Return of the elevated mitotic rate to base level takes 18 days from the time the last injection of PCN was administered. During this time the number and the average volume of liver cells increases by 28% and 30%, respectively. The dry weight of liver and tetraploid nuclei increase in number, whereas RNA- and protein content remains unchanged. All parameters have reached the base line after 4 - 6 weeks following the last injection of PCN. No histological changes were observed after multiple doses of PCN that cause hyperplasia and hypertrophy of liver tissue. Hypertrophy of liver cells follows the observed hyperplasia and therefore is not expected to be the cause of the hyperplastic processes.