The classic rule stating that restricting intake by 3500 kcal/wk will lead to a 1-lb/wk rate of weight loss has come under intense scrutiny. Generally not a component of most weight loss prediction models, the "early" rapid weight loss phase may represent a period during which the energy content of weight change (ΔEC/ΔW) is low and thus does not follow the classic "rule." The current study tested this hypothesis. Dynamic ΔEC/ΔW changes were examined in 23 Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Study overweight men and women evaluated by dual-energy x-ray absorptiometry during weight loss at treatment weeks 4 to 24. Changes from baseline in body energy content were estimated from fat and fat-free mass. Repeated-measures analysis of variance was used to determine if ΔEC/ΔW changed significantly over time. The evaluation was expanded with addition of the Kiel 13-week weight loss study of 75 obese men and women to test with adequate power if there are sex differences in ΔEC/ΔW. The analysis of variance CALERIE time effect was significant (P < .001), with post hoc tests indicating that ΔEC/ΔW (kilocalories per kilogram) increased significantly from week 4 (X ± SEM; 4, 858 ± 388) to 6 (6, 041 ± 376, P < .01) and changed insignificantly thereafter; ΔEC/ΔW was significantly larger for Kiel women (6, 804 ± 226) vs men (6, 119 ± 240, P < .05). Sex-specific dynamic relative changes in body composition and related ΔEC/ΔW occur with weight loss initiation that extend for 1 month or more. These observations provide new information for developing energy balance models and further define limitations of the 3500-kcal energy deficit → 1-lb weight loss rule.