Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of lipoproteinaceous material in the alveolar space. Serum lactate dehydrogenase (LDH) has been noted to be elevated in patients with PAP in previous studies. We sought to extend this observation in a series of patients with PAP by looking at total serum LDH concentrations and LDH isoenzyme fractions measured before and after whole lung lavage. Total LDH and LDH isoenzymes were also determined in the lavage effluent. Total serum LDH was elevated before lavage in 10 of 16 patients. Prelavage serum LDH and prelavage alveolar-arterial O2 gradient showed a significant correlation (r = 0.62, p less than 0.05). A decrease in serum LDH was found after lavage in all patients in whom postlavage data was available (paired t test, p less than 0.01, n = 11), although the magnitude of this decrease varied considerably. The isoenzyme pattern before lavage was isomorphic, and this pattern was unchanged after whole lung lavage. This was in marked contrast to the LDH isoenzyme pattern observed in the lavage effluent, which showed a lower percent LDH1 and LDH2 and a higher percent LDH3, LDH4, and LDH5 when compared with the corresponding prelavage isoenzyme percentages for serum (unpaired t test, p less than 0.001). There was no correlation between the total serum LDH concentration and the total lavage LDH concentration. These data confirm that elevated serum LDH is a common finding in PAP. Furthermore, the LDH elevation found consistently in the alveolar fluid points to this as the source of the serum LDH.(ABSTRACT TRUNCATED AT 250 WORDS)