The effect of penicillamine administration on pyridoxal enzyme activities of rats was investigated. Penicillamine reduced the activities of glutamate decarboxylase [EC 4.1.1.15] in brain and ornithine aminotransferase [EC 2.6.1.13] in small intestine, and increased those of ornithine and tyrosine aminotransferases [EC 2.6.1.5] in liver. It did not cause much change in the activities of kidney ornithine aminotransferase or liver aspartate or alanine aminotransferases [EC 2.6.1.1 and 2]. Changes in these activities were prevented by simultaneous injection of pyridoxine. A marked increase in activity of the inactivating enzyme for pyridoxal enzymes was also observed in the small intestine of animals treated with penicillamine. Treatment of adrenalec-tomized rats with penicillamine unaffected liver ornithine aminotransferase activity. The possible interrelation between penicillamine and these pyridoxal enzymes is discussed in this paper.