Understanding the effects of inbreeding and genetic drift within populations and hybridization between genetically differentiated populations is important for many basic and applied questions in ecology and evolutionary biology. The magnitudes and even the directions of these effects can be influenced by various factors, especially by the current and historical population size (i.e., inbreeding rate). Using Drosophila littoralis as a model species, we studied the effect of inbreeding rate over a range of inbreeding levels on 1) mean fitness of a population (relative to that of an outbred control population), 2) within-population inbreeding depression (reduction in fitness of offspring from inbred vs. random mating within a population), and 3) heterosis (increase in fitness of offspring from inter-population vs. within-population random mating). Inbreeding rate was manipulated by using three population sizes (2, 10, and 40), and fitness was measured as offspring survival and fecundity. Fast inbreeding (smaller effective population size) resulted in greater reduction in population mean fitness than slow inbreeding, when populations were compared over similar inbreeding coefficients. Correspondingly, populations with faster inbreeding expressed more heterosis upon inter-population hybridization. Inbreeding depression within the populations did not have a clear relationship with either the rate or the level of inbreeding.