Available evidence indicates that protein incorporation by amphibian oocytes is mediated through a process of micropinocytosis. Oocytes incubated under our standard conditions sequester protein at a constant rate for at least 24 hours and appear to maintain approximately the same level of micropinocytosis as that observed in situ. Protein uptake is markedly sensitive to temperature and the ionic composition of the medium, with calcium being a particularly important component. Magnesium, phosphate, and additional energy sources are of only minor significance. Based on these observations, several slightly improved reformulations of the standard incubation medium are provided.