Pleural fluid levels of the cancer antigen 15-3 (CA15-3) detected by monoclonal antibodies (115D8 and DF3) were determined in 40 patients with carcinomatous pleural effusions and in 41 patients with tuberculous pleural effusions. Using a cut off level of 16 U/ml, 15 of the 40 carcinomatous fluids but none of the 41 tuberculous fluids were positive. Pleural fluid levels of CA15-3 were not correlated with those of carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9). Combined assay of CEA and CA15-3, or CA19-9 and CA15-3, increased the positive rate from 79 to 82% and from 67 to 73%, respectively. Measurement of pleural fluid CA15-3 levels are less useful in separating carcinomatous from tuberculous effusions than is measurement of CEA or CA19-9.