The time course of phagocytosis and phagosome-lysosome fusion (PLF) in lung and peritoneal macrophages (LMs and PMs) was measured. Lysosomes in unelicited hamster LMs and PMs were labeled with lucifer yellow. Macrophages then phagocytized heat-killed Saccharomyces cerevisiae (yeast) and were evaluated at several time points for the degree to which yeast particles were adherent vs. internalized and for the presence or absence of PLF as based on the presence or absence of lucifer yellow in yeast-containing phagosomes. A three-compartment model (adherent, ingested, fused) of independent phagocytosis and PLF was developed; the number of yeast particles in each compartment was counted, and rate constants for ingestion and fusion were determined. Comparison of rate constants showed that ingestion was significantly faster in PMs (0.047 +/- 0.005 min-1) than in LMs (0.016 +/- 0.005 min-1) (mean +/- pooled SEM; P less than 0.001). Similarly, PLF was significantly faster in PMs (0.109 +/- 0.013 min-1) than in LMs (0.046 +/- 0.013 min-1) (P less than 0.003).