Accumulated evidence suggested the occurrence of the following sequence of events in nidation in the rat: An oestrogen-surge, occurring on day L3 of pregnancy, releases histamine in the uterus; the liberated histamine stimulates the progestational endometrium, inducing decidualization. Since an oestrogen-surge occurs also during pseudopregnancy, the same sequelae, culminating in decidualization, are to be invariably expected. The present study was undertaken to determine the basis for the rarity of spontaneous decidualization in the pseudopregnant rat. Measurement of day to day changes in the histamine content of the rat uterus confirmed the occurrence of histamine-release following the oestrogen-surge of pregnancy. During pseudopregnancy, however, following the histamine decline after oestrus, a high histamine level is not re-established as in pregnancy but the histamine content remains low and no release is observed after the oestrogen-surge of pseudopregnancy. Supplementing the surge oestrogen with exogenous oestradiol or oestriol in doses as great as 40 μg failed to induce a significant degree of decidualization in the pseudopregnant rat, indicating that no significant release of histamine was induced. The rarity of spontaneous decidualization in the pseudopregnant rat therefore is due to the absence of a pool of histamine amenable to release by oestrogen. It is, therefore, apparent that hormonal influences on the uterus are not identical in pseudopregnancy and in pregnancy.