The role of high-fat diets in weight gain and obesity has been questioned because of inconsistent reports in the literature concerning the efficacy of ad libitum low-fat diets to reduce body weight. We conducted a meta-analysis of weight loss occurring on ad libitum low-fat diets in intervention trials, and analysed the relationship between initial body weight and weight loss. We selected controlled trials lasting more than 2 months comparing ad libitum low-fat diets with a control group consuming their habitual diet or a medium-fat diet ad libitum published from 1966 to 1998. Data were included from 16 trials with a duration of 2-12 months, involving 1728 individuals. No trials on obese subjects fulfilled the inclusion criteria. The weighted difference in weight loss between intervention and control groups was 2.55 kg (95% CI, 1.5-3.5; P < 0.0001). Weight loss was positively and independently related to pre-treatment body weight (r=0.52, P < 0.05) and to reduction in the percentage of energy as fat (0.37 kg/%, P < 0.005) in unweighted analysis. Extrapolated to a BMI of about 30 kg/m2 and assuming a 10% reduction in dietary fat, the predicted weight loss would be 4.4 kg (95% CI, 2.0 to -6.8k kg). Because weight loss was not the primary aim in 12 of the 16 studies, it is unlikely that voluntary energy restriction contributed to the weight loss. Although there is no evidence that a high intake of simple sugars contributes to passive overconsumption, carbohydrate foods with a low glycaemic index may be more satiating and exert more beneficial effects on insulin resistance and cardiovascular risk factors. Moreover, an increase in protein content up to 25% of total energy may also contribute to reducing total energy intake. In conclusion, a low-fat diet, high in protein and fibre-rich carbohydrates, mainly from different vegetables, fruits and whole grains, is highly satiating for fewer calories than fatty foods. This diet composition provides good sources of vitamins, minerals, trace elements and fibre, and may have the most beneficial effect on blood lipids and blood-pressure levels. A reduction in dietary fat without restriction of total energy intake prevents weight gain in subjects of normal weight and produces a weight loss in overweight subjects, which is highly relevant for public health.