Caenorhabditis elegans typically feeds on rotting fruit and plant material in a fluctuating natural habitat, a boom-and-bust lifestyle. Moreover, stage specific developmental responses to low food concentration suggest that starvation-like conditions are a regular occurrence. In order to assess variation in the C. elegans starvation response under precisely controlled conditions and simultaneously phenotype a large number of individuals with high precision, we have developed a microfluidic device that, when combined with image scanning technology, allows for highthroughput assessment at a temporal resolution not previously feasible and applied this to a large mapping panel of fully sequenced intercross lines. Under these conditions worms exhibit a markedly reduced adult lifespan with strain-dependent variation in starvation resistance, ranging from <24 hours to ~120 hours. Genome-wide mapping of the responses of more than 7,855 individuals identified four quantitative trait loci (QTL) of large effects. Three of these loci are associated with single genes (ash-2, exc-6, and dpy-28) and the fourth is a ~26 KB region on Chromosome V encompassing several genes. Backcross with selection confirmed the effect of the Chromosome V locus. Segregating natural variation for starvation response in this species suggests that different isolates may use different strategies (facultative vivipary versus reproductive diapause) for dealing with extreme food deprivation.