Commercial airline cockpit crews flying transoceanic routes were tested repeatedly with a battery of cognitive tests implemented on a lap-top microcomputer. Testing was conducted before departure and during the early, middle, and late periods in flight on the outbound leg of four flight pairings.The same tests were administered on the return leg(s) of each flight pairing but, just prior to final administration of the tests, six minutes of moderate resistance exercise was undertaken by the Captain and one other pilot (either the First or Second Officer). The remaining officer substituted a walk around the aircraft cabin for exercise and served as a control. The same Flight Captain was available for testing on all flights (N = 22), but due to scheduling requirements, the same First and Second Officers were available for 4-8 flights each.Comparisons were made between the two exercise conditions over all test sessions, but no statistical relationships were found. It appeared that effects were masked by the scatter caused by the individual differences in the various performances of the eight different First and Second Officers who alternated through the four flight segments. However, indicators were present in the data of the Flight Captain which supported the hypothesis that exercise had a positive impact on pilot performance. Because the Flight Captain was followed over all his flight segments for a total of 8 months of testing (and which involved some 65 test cycles), the data were treated as a single subject time-series study. In this analysis, two of the six Automated Performance Test System (APTS) tests (Turnage, Kennedy, Smith, Baltzley, & Lane, 1992) (those representing higher order cognitive skills) were statistically significant (p < .05 for Code Substitution and p < .01 for 4-Choice Reaction Time) when comparisons were made between either “middle” or “late” in hop segments versus after “layover” or after “exercise.”Pilot testing in the future is planned to broaden our experience using this paradigm and to replicate these findings in additional individuals.