Seventeen healthy volunteers (10 women and 7 men, aged 29-68) were flown from London to San Francisco between 20 November 1985 and 25 January 1986 and remained there for 14 days prior to flight home. Subjects took melatonin (N = 8, 5 women, 3 men) or placebo in a double-blind design, at 18.00h local time for three days before the return flight and at bedtime (22.00-24.00h) in Great Britain for four days. For three days before departure and on days 1-7,14,15, 21 and 22 after their return subjects collected 6-hourly sequential urine samples and kept a daily sleep log. They recorded mood and oral temperature 2 hourly and performed logical reasoning and letter cancellation tests 4 hourly from 08.00h (or wake up time) to 24.00h (or bedtime) whichever was the earlier. Urine was also collected for 48 h prior to departure from the U.S.A‥ On day 7 after their return subjects rated ‘jet lag’ (10 cm visual analogue scale—VAS) from 0 (insignificant) to 100 (very bad). Melatonin significantly improved ‘jet lag’ (p= 0.009). Comparisons by ANOVA between jet-lagged placebo subjects (N = 7) and melatonin (N = 8) showed decreased sleep latency with melatonin (p= 0.0397) which correlated positively with jet lag ratings, p< 0.001. Sleep quality was significantly improved in the melatonin group and correlated negatively with jet-lag ratings (p<0.001). No important differences were found in temperature, or performance data. Baseline differences were present in some performance ratings but no other variables. Melatonin treated subjects tended to be more alert than placebo subjects, especially at bedtime. They were also less depressed. Endogenous melatonin and Cortisol rhythms resyn-chronized more rapidly in melatonin subjects (p= 0.0216 and p= 0.0299 respectively, absolute acrophase shifts). Cortisol rhythms indicated adaptation to U.S.A. time in 14 days. These data suggest that MT can alleviate jet-lag after Eastward flight over eight time zones. Presumably its affects are primarily on sleep latency, quality, and directly or indirectly on some hormonal rhythms.