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Tritium-labeled trandolaprilate (RU 44403), the active diacid form of the potent and long-acting angiotensin-converting enzyme (ACE) inhibitor trandolapril, has been evaluated as a new autoradiographic marker for the enzyme. The characteristics of 3H-trandolaprilate binding were first determined autoradiographically in tissue sections from rat brain (caudate-putamen) and kidney. 3H-Trandolaprilate binds saturably to these tissues, and with very high affinity (Kd values, 0.36 and 0.13 nM, respectively), and appears to show good selectivity for the enzyme. Due to its high affinity (approximately 100 times that of captopril), the performance of 3H-trandolaprilate as an autoradiographic marker is comparable to that of the recently described 125I-labeled derivative of lisinopril (125I-351A). Saturation and displacement studies in serial sections from a variety of central and peripheral tissues confirmed that the specificity of labeling was similar throughout. The anatomical distribution of ACE visualized with 3H-trandolaprilate in these tissues was close to that described for 3H-captopril and 125I-351A with some minor differences which might arise from difference in the specificity of the ligands.