Abstract. There is mounting evidence consistent with a general role of positive selection acting on the Drosophila melanogaster X-chromosome. However, this positive selection need not necessarily arise from forces that are adaptive to the organism. Nonadaptive meiotic drive may exist on the X-chromosome and contribute to forces of selection. Females from a reference D. melanogaster line, containing the X-linked marker white, were crossed to males from 49 isofemale lines established from seven African and five non-African natural populations to detect naturally occurring meiotic drive. Several lines exhibited a departure from expected Mendelian transmission of X-chromosomes to the third generation (F 2 ) offspring, particularly those from hybrid African male parents. F 2 viability was not correlated with skewed chromosomal inheritance. However, a significant difference in viability between cosmopolitan and tropical African crosses was observed. Recombination analysis supports the presence of a male-acting meiotic drive element near the centromeric region of the X-chromosome and putative recessive autosomal drive suppression. There is also evidence of another female-acting drive element linked to white. The possible role meiotic drive may contribute in shaping levels of genetic variation in D. melanogaster, and additional ways to test this hypothesis are discussed.Key words. Adaptation, Drosophila melanogaster, meiotic drive, positive selection, sex ratio, viability, X-chromosome.Received January 11, 2005. Accepted March 20, 2005 Prior to the 1970s, meiotic drive was widely documented in Drosophila species, including D. melanogaster, and was generally appreciated to be a potent evolutionary force with the capacity to impact patterns of genetic variation in natural populations . Since the early 1990s, molecular evidence of the widespread role of selection in D. melanogaster and other species has accumulated (for reviews, see Andolfatto 2001a; Aquadro et al. 2001; Schlöt-terer 2002). Several investigations have found evidence consistent with positive selection, sometimes population specific, on the D. melanogaster X-chromosome (e.g., Aquadro 1992, 1994;Aguadé 1999;Begun and Whitley 2000;Langley et al. 2000;Andolfatto 2001b;Andolfatto and Przeworski 2001;Glinka et al. 2003; Kauer et al. 2003a,b). Despite this early understanding of meiotic drive and mounting evidence for frequent positive selection, in recent decades the role meiotic drive may play in contributing to the effects of positive selection within and between populations has largely been ignored (with some exceptions; e.g., Palopoli and Wu 1996;Malik and Henikoff 2001;Derome et al. 2004). Rather than considering selfish genetic elements, explicit or implicit conclusions that evidence of selective-sweeps reflects organismal adaptation, perhaps to novel environments, have often been made. Here we revisit the potential role meiotic drive has as an evolutionary force and test for the frequency of susceptibility to X-linked meiotic drive in natural populations...