Abstract Toxicologic aspects of long-term therapy with the gallstone-dissolving agent, chenodeoxycholic acid (CDC) are under study in the baboon. Eighteen animals, subdivided into low (20 mg. per kilogram per day), incremental (18 to 38 mg. per kilogram per day), and high (38 mg. per kilogram per day) dose groups were fed CDC daily for 8 to 15 months. During that period they maintained an appearance of excellent, unchanged health and behavior indistinguishable from that of eight control animals. However, 15 of the 18 CDC-fed animals showed significant elevations of monthly serum glutamic pyruvic transaminase-serum glutamic oxalacetic transaminase determinations, and 14 of the 18, from all dose groups, developed significant focal histologic changes in serial liver biopsies. Histologic changes are similar to those described for lithocholic acid toxicity and correlate with an elevated percentage of chenodeoxycholic acid and, particularly, with lithocholic acid (8 to 14 percent) in gallbladder bile of the CDC-fed animals. A few CDC-fed animals showed histologic changes without enzymatic changes and vice versa. To date none of the focal hepatic lesions appears irreversible; it is too early to determine whether continued CDC feeding results in progression, stabilization, or regression of changes. More intensive surveillance of human subjects receiving chenodeoxycholic acid is indicated.