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The role and timing of physical therapy following axillary dissection for melanoma, or in conjunction with modified radical mastectomy has not been extensively studied. A prospective randomized clinical trial was carried out over an 18-month period in the Surgery Branch, National Cancer Institute (NCI) and Department of Rehabilitation Medicine, Clinical Center, in which patients were assigned to receive one of two post-operative physical therapy regimens. Patients were assigned to receive graduated increases in allowed range of motion (ROM), either beginning on postoperative day 1 (early) or day 7 (delayed). All patients were advanced to full pain-free ROM when the suction catheters were removed. A total of 36 patients with 40 axillary dissections (19 for melanoma, 21 for breast cancer) were included in this study. Patients randomized to receive early motion had more total wound drainage (805 ± 516 cc vs. 420 ± 301 cc, p < 0.01), more days of drainage (10.3 ± 5.3 vs. 6.2 ± 2.7, p < 0.01), and later postoperative day of discharge (12.8 ± 5.1 days vs. 9.2 ± 4.0 days, p < 0.02) than did patients who started motion on day 7. Wound complications including infection and small areas of skin breakdown occurred more frequently in the early group (seven patients vs. one patient, p < 0.02). No significant differences in the per cent of patients achieving functional ROM could be identified between these two groups at one, three or six months after operation. Transient serratus anterior palsy (12 patients) and latissimus dorsi palsy (2 patients) occurred in approximately 30% of all patients, regardless of group (breast vs. melanoma, early vs. delayed), but returned to normal in all patients. The early institution of flexion and abduction exercises following axillary dissection thus appears to have a deleterious effect on wound healing and drainage. Adequate functional ROM is attained in all patients with a minimum of complications when active motion exercises are delayed for up to 7 days after axillary dissection.