In the compound ascidianBotryllus schlosseri, phagocytes change their morphology and frequency during the colonial blastogenic cycle. In the regression phase, characterized by intense phagocytosis, zooids of the old generation are progressively resorbed, the frequency of hyaline amoebocytes falls abruptly, and the frequency of macrophage‐like cells increases significantly. Moreover, the hyaline amoebocytes engulf foreign materials, withdraw their cytoplasmic projections, and change their shape from flat and fusiform to spherical or ovoidal: all these processes suggest that hyaline amoebocytes represent the precursors of macrophage‐like cells. During regression, a significant increase in blood levels of hydrogen peroxide and acid phosphatase is observed, in agreement with data obtained inin vitroexperiments showing an increase in reactive oxygen metabolite production, nitrite ion release, and acid phosphatase secretion associated with phagocytosis.