A sandwich enzyme-linked immunosorbent assay for measuring serum transforming growth factor-α levels was developed with monoclonal IgM and polyclonal IgG antihuman transforming growth factor-α antibodies and a system to amplify the activity of the conjugated enzyme. The assay detected serum transforming growth factor-α levels as low as 5 pg/ml. Serum transforming growth factor-α levels were below the detection limit of the assay in 19% of healthy adults, with a mean (± S.D.) detectable level of 22.0 ± 16.7 pg/ml. In 13 patients who underwent partial hepatectomy, serum transforming growth factor-α levels were determined serially after surgery. The levels were increased within 28 days of surgery in all the patients, with a mean maximal level of 118.2 ± 90.8 pg/ml. The maximal level achieved in each case correlated significantly with the resected volume of the liver and the increased volume of the remaining liver 28 days after hepatectomy (r = 0.59, p < 0.05, and r = 0.71, p < 0.005, respectively). In contrast, serum transforming growth factor-α levels showed no increase after laparotomy for nonhepatic surgery. Serum transforming growth factor-α levels may vary depending on the regenerative stimulus and reflect the degree to which liver regeneration will occur in patients after partial hepatectomy. (HEPATOLOGY 1993;18:304–308).