A plasma membrane ectoenzyme in mammalian cells, 5'-nucleotidase, was evaluated as a marker for ovarian carcinoma. Activities of this enzyme were determined in homogenates from normal (N = 17) and malignant ovaries (N = 17), as well as in the sera from control women (N = 35), ovarian cancer patients with active disease (N = 24), and those in clinical remission (N = 9). A significant reduction of the activity of 5'-nucleotidase was observed in tumor homogenates compared with homogenates from normal ovaries. Levels of this enzyme in the sera of ovarian cancer patients were higher than in control women, suggesting the possibility of shedding of this enzyme from the tumor cell surface to the systemic circulation of the host. The diagnostic value of serum 5'-necleotidase levels was compared with another enzyme marker for ovarian carcinoma, viz. serum glycoprotein:galactosyltransferase. The upper limit of normal was set at 2 SD higher than the normal mean. Elevation of serum 5'-nucleotidase was observed in 12/24 (50%) patients with active disease, and 1/9 (11%) patients with clinical remission. In contrast, serum glycoprotein:galactosyltransferase was elevated in all the serum samples from patients with active disease and in none of those with clinical remission. There was some correlation between the serum levels of 5'-nucleotidase and those of glycoprotein:galactosyltransferase (0.01 less than P less than 0.05). Elevation of 5'-nucleotidase in the serum of these patients was not due to liver metastasis. Serum 5'-nucleotidase levels seem to correlate with disease status in some ovarian carcinoma patients, but in general it is inferior to serum glycoprotein:galactosyltransferase as a tumor marker.