Recent studies have shown a close association between byssinosis and airborne endotoxin concentrations. Endotoxin might induce byssinosis through the release of biochemical mediators as the broncheoalveolar surface. Alpha-1-antitrypsin (alpha-1-A) which neutralizes enzymes released by granulocytes is known to be important. This study evaluates the possible importance of alpha-1-A concentration and the heterozygosity (Pi-S and Pi-Z alleles), in the prevalence of byssinosis and familial allergy. 253 cotton workers were interviewed and clinically studied to identify persons with the cotton lung disease, byssinosis, and atopic disease. Serum was available for alpha-1-A concentration determination in 226 individuals, and for Pi phenotyping in 206. The overall prevalence of byssinosis was 30/226 (13%). In the group with alpha-1-A < or = 35 mumol l-1 the prevalence was 5/18 (28%), versus the prevalence 25/208 (12%) in the group with alpha-1-A > 35 mumol l-1 (p < 0.1, Fishers exact test). MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM-group: 3/8 (38%) and 25/187 (13%), p < 0.1, Fishers exact test. An association between MZ-phenotype and familial allergy was found: 4/8 (50%) contra 23/187 (12%), p < 0.05, Fishers exact test. In a logistic regression model controlling for confounding by endotoxin, tobacco exposure, sex, and age, the odds ratio for byssinosis in the MZ-phenotype group was significantly elevated 5.8 (1.1-30.3). Odds ratio for familial allergy was also significantly elevated in the MZ-group 2.8 (1.3-5.9).(ABSTRACT TRUNCATED AT 250 WORDS)