Results were provided of studies of a protein factor associated with experimentally induced silicosis in rats. The response to treatment with antisilicotic/rat lung rabbit serum (ASLS) was evaluated. A serum protein factor (SPF) was noted in 82.8% of the silicotic rats. The factor was not noted in normal or control rats. Rats were injected intratracheally with silica (14808607) (SiO2), calcium- fluoride (7789755) (CaF), silica plus sodium-fluoride (7681494) (Na2F), or silica plus aluminum-hydroxide (21645512) (Al(OH)3) dusts. Serum samples were collected and assayed for SPF. The percentages of SiO2, CaF, SiO2 plus Na2F, and SiO2 plus Al(OH)3 dose rats that were positive for SPF were 82.98, 25, 20, and 36.35%, respectively. Rats were administered SiO2 dust and serum samples were collected 7 to 210 days post dosing and assayed for SPF. SPF was not detected until after 15 days. After 15 days the rate of SPF positivity increased with increasing time after exposure. A similar experiment was done to correlate SPF positivity with indicators of silicosis severity such as wet lung weight, lung collagen content, and extent of fibrosis. The rate of SPF positivity increased with increasing severity of silicosis. Alveolar macrophages recovered from untreated and SiO2 treated rats were incubated with ASLS and antisilicotic/rat alveolar macrophage serum (ASMS). Both ASLS and ASMS were cytotoxic and caused the macrophages to agglutinate. Other rats were administered SiO2 and bronchoalveolar lavage was performed 15 to 130 days later. Lavage fluid from SiO2 treated rats contained larger numbers of macrophages than fluid from untreated rats. The number of macrophages increased with increasing time after SiO2 exposure. The authors conclude that alveolar macrophage destruction appears to play an important role in experimental silicosis.