A high throughput calcium flux assay was developed for the LabChip?microfluidic system. The system accesses samples from a microplate, mixes the samples with cells flowing through a microchannel and reads out cellular responses using fluorescence detection. Calcium responses resulting from G-protein coupled receptor activation were measured. The ability to conduct screens for GPCR agonists and antagonists was demonstrated by screening for agonists and antagonists of the m1-muscarinic receptor mediated calcium response in CHO cells. The LabChip?system uses as few as 50-100 cells per sample and less than 10 nl of sample and 10 nl of agonist per measurement. Because of the low cellular and reagent consumption, and high data quality obtained with the microfluidic device, the LabChip?system should be widely applicable in high throughput screening.