SummaryPhenotypic changes in murine alveolar macrophages have been described in response to vaccination with irradiated cercariae and to a subsequent challenge with normal parasites. Flow cytometric analysis was used to quantify the proportions of cells strongly positive for a number of macrophage surface markers, detected by a panel of monoclonal primary antibodies and fluorescent secondary antibodies. The proportion of Ia+macrophages sampled by bronchoalveolar lavage increased 5‐fold over days 14 to 28 post‐vaccination. This upregulation of Ia was accompanied by a sharp decrease in F4/80 expression between days 14 and 21. The low percentage of F4/80* cells persisted for several weeks after vaccination, and no further change was stimulated by challenge parasites. These altered characteristics are consistent with the ‘activation phenotype’ induced by other infectious agents. After challenge of immune mice, further changes in macrophage phenotype were slight compared to the responses elicited by vaccination, or to those induced in the challenge control group; la expression increased to about three times normal levels. The phenotypic changes correspond both in magnitude and timing with the pattern of alveolar macrophage activation determined in a previous study. The limited changes in phenotype of alveolar macrophages from immunized mice after challenge could indicate that these cells become refractory to reactivation. Overall, the altered macrophage phenotype after vaccination and challenge provides circumstantial evidence for the action of cytokines, particularly interferon‐gamma, in lung‐phase immunity to s