An extensive study of helium isotopes in fluids collected from surface springs, fumaroles and wells across the northern Basin and Range Province reveals a systematic trend of decreasing 3He/4He ratios from west to east. The western margin of the Basin and Range is characterized by mantle-like ratios (6-8 Ra) associated with active or recently active crustal magma systems (e.g. Coso, Long Valley, Steamboat, and the Cascade volcanic complex). Moving towards the east, the ratios decline systematically to a background value of ∼0.1 Ra. The regional trend is consistent with extensive mantle melting concentrated along the western margin and is coincident with an east-to-west increase in the magnitude of northwest strain. The increase in shear strain enhances crustal permeability resulting in high vertical fluid flow rates that preserve the high helium isotope ratios at the surface. Superimposed on the regional trend are "helium spikes", local anomalies in the helium isotope composition. These "spikes" reflect either local zones of mantle melting or locally enhanced crustal permeability. In the case of the Dixie Valley hydrothermal system, it appears to be a combination of both.