Our objective was to determine the effects of long-lasting endurance events on the energy cost of running (C(r)), and the role of maximal oxygen uptake (VO(2max)), its fractional utilisation (F) and C(r) in determining the performance. Ten healthy runners (age range 26-59 years) participated in an ultra-endurance competition consisting of three running laps of 22, 48 and 20 km on three consecutive days in the North-East of Italy. Anthropometric characteristics and VO(2max) by a graded exercise test on a treadmill were determined 5 days before and 5 days after the competition. In addition, C(r) was determined on a treadmill before and after each running lap. Heart rate (HR) was recorded throughout the three laps. Results revealed that mean C(r) of the individual laps did not increase significantly with lap number (P = 0.200), thus ruling out any chronic lap effect. Even so, however, at the end of lap 3, C(r) was 18.0% (P < 0.001) greater than before lap 1. In addition, a statistically significant acute lap effect on C(r) was observed at the end of the second and third laps (by 11.4 and 7.2%, respectively). The main factors determining performance were VO(2max), F, as estimated from the average HR, and the average C(r-mean) throughout the three laps; the grand average speed over the three laps being described by v (end-mean) = F × VO(2max) × C(r-mean)(-1). We concluded that (1) the substantial increase of C(r-mean) during the competition yields to marked worsening of the performance, and (2) the three variables F, VO(2max) and C(r-mean) combined as described above explaining 87% of the total competition time variance.