Sodium-n-butyrate affects the length of the mitotic cycle of Physarum polycephalum. Application during S- or early G2-period results in a delay of the subsequent mitosis, whereas application later in the cycle has no delaying effect. Interestingly, the second mitotic cycle after application is considerably shortened when butyrate has been administered during S- or early G2-period of the preceding cycle. In comparison, other homologous short-chain fatty acids were tested; the retarding effect on mitosis increases with the number of carbon atoms, although only butyrate can shorten the second mitotic cycle. It is shown that butyrate causes an immediate depression of synthesis of DNA, RNA and protein. After a certain time-interval the plasmodium overcomes the butyrate block. DNA synthesis is fully recovered and the inhibition of RNA and protein synthesis is even overcompensated until the next mitosis, as reflected by elevated levels of RNA and protein.