Macrophages secrete substances that stimulate angiogenesis and mitogenesis at wound sites. To test whether metabolic characteristics of the wound such as high lactate concentration and low pH may regulate the expression of these substances, macrophages were cultured in lactalbumin hydrolysate and then in increasing concentrations of lactate, pyruvate, and hydrogen ions, and cell-free supernatants were collected. Cultures incubated in concentrations of lactate approximating those observed in wounds secreted an angiogenesis factor or factors, but cultures incubated in equivalent concentrations of pyruvate or at pH 6.2 did not. These observations seem to be specific to macrophages because capillary endothelial cells and fibroblasts failed to secrete an angiogenesis factor when cultured under hypoxic conditions or in high concentrations of lactate. None of these conditions changed the expression of macrophage mitogens.