Natural convection experiments were performed for an enclosure of square cross section containing either a single fluid or two immiscible fluids in a layered configuration. The two vertical walls of the cross section were respectively heated and cooled, while the two horizontal walls were adiabatic. The single-fluid experiments, performed with distilled water and with n-hexadecane paraffin (Pr = 5 and 39.2, respectively), yielded Nusselt numbers whose Rayleigh and Prandtl number dependences were perfectly correlated by a single dimensionless group. These singlefluid results were used as baseline information for the development of methods to predict the heat transfer in two-fluid layered systems. To test the utility of the predictive methods, experiments were carried out for water-hexadecane systems in which the position of the interface separating the liquids was varied parametrically. It was found that the experimentally determined, two-layer Nusselt numbers were in excellent agreement with the predicted values. The prediction methods are not limited to the particular fluids employed here, nor do they require additional experimental data for their application.