The estrogen phenol A-ring metabolism was investigated in the first trimester placenta using radioenzymatic techniques. In untested explants cultured for 16h, estrogen hydroxylase (EH) but not catechol-O-methyl transferase (COMT) activity was increased significantly 1.8-fold (P < 0.05). Cultures made in the presence of chemoprotectors, 25 μM of 1-phenylazo-2-naphtol (Sudan I) and coumarin but not 2(3)-tert-butyl-4-hydroxy anisole (BHA) caused a significant increase in EH activity, 1.8- and 2.2-fold, respectively (P < 0.05). This was coupled with a significant, P < 0.05, increase in the COMT activity by 25 μM of all three chemoprotectors, BHA, Sudan I, and coumarin, 2.7-, 2.3-, and 2-fold respectively. The carcinogens benzo(a)pyrene and 20-methylcholanterene at 50 μM concentration, however, had no effect upon both enzymes' activity. Finally, the two enzymes's activities were correlated under the experimental conditions tested. Except for zero time where no correlation was found (r2 = 0.3), in all other experimental conditions, a significant (r2 = 0.75) correlation was observed. In conclusion, EH and COMT enzyme activities appear to undergo a coordinated induction in cultured placental explants in the first trimester. The implications of catechol metabolism for embryonal development are discussed. © 1990.