Leukocyte alkaline phosphatase (LAP) activity was determined in normal subjects, and in untreated, symptomatic patients with primary hypothyroidism or thyrotoxicosis. The means +/- 1 SD of (n) subjects were, respectively: 61.7 +/- 27.5 (16), 149.9 +/- 56.3 (9) and 96.9 +/- 27.7 (9). The mean LAP values of the hypothyroid and thyrotoxic groups were significantly different from that of the normal group (P less than .01). Values were above the normal range (20 to 120) in seven of the nine hypothyroid patients. LAP values were in the upper half of the normal range in eight of the nine thyrotoxic patients. In the two hypothyroid patients studied at 24-hour intervals, LAP activity was altered markedly within 48 hours of initiation of thyroxine therapy, 25 micrograms daily. In five hypothyroid patients followed for several months after initiating thyroxine replacement, LAP levels were essentially normal within 1 to 2 months. In the thyrotoxic patients, LAP values declined within the first month of medical management, but tended to remain within the normal range.