Serum levels of protein 1 (P1), a Clara cell secretory protein, were studied in 942 healthy subjects in relation to sex, age, and smoking habits and in 117 patients with bacterial pneumonia in relation to prognosis. P1 values in bacterial pneumonia patients at disease onset were compared with those in 234 healthy control subjects matched by sex and age. P1 values in healthy males were highest in those 30 to 39 yr of age and highest in healthy females > or = 70 yr of age but lowest in those 30 to 49 yr of age. P1 values in healthy males were significantly higher than those in females in the 30- to 39-yr age group (p < 0.05). Male smokers showed higher P1 values than nonsmokers, but without a significant difference. P1 values in patients with pneumonia were significantly lower than in control subjects (p < 0.0001). P1 values were significantly lower in patients treated with a respirator than in in patients treated without a respirator (p < 0.05). In 59 patients, whose P1 values could be followed up until the outcome of pneumonia, all 37 recovered patients showed significantly increased P1 values after recovery (p < 0.001), and all 22 who died of their illness showed significantly decreased P1 values just before death (p < 0.01). We thus conclude that P1 serum levels were significantly affected by sex and by the degree of seriousness in bacterial pneumonia.