We have analyzed noble gas isotopes in 19 mud gas samples from 116--3943 m borehole depth of the San Andreas Fault Observatory at Depth (SAFOD) Main Hole in the context of origin and spatial variability of fluids occurring at seismogenic depths. The measured 3He/4He ratios range between 0.40 and 1.02 Ra (Ra is the atmospheric 3He/4He ratio of 1.39 ¿ 10-6), with 4He/20Ne values between 0.33 and 4.92, revealing a mixture of three components to the total helium: (1) atmospheric helium, (2) helium with a crustal signature, and (3) mantle-derived helium. The air-corrected 3He/4He ratios fall between 0.2 Ra and 0.9 Ra. Samples from the 2117--3196 m depth show a relatively constant helium isotope composition (0.35--0.46 Ra), indicating that ~5% of the helium in this section the Pacific Plate is derived from the mantle. The contribution of mantle-derived helium increases slightly in the transition from the Pacific Plate to the North American Plate and reaches maximal values of ~12% on the North American Plate (below ~3500 m borehole depth). On the basis of our observations, we suggest that the San Andreas Fault plays a role for fluid flux from greater depths, but higher amounts of mantle-derived fluids rise up through other, more permeable faults, situated on the North American Plate of the San Andreas Fault Zone (SAFZ). Lateral fluid dispersion at shallow depths through permeable country rock of the North American Plate may explain the observed increase in 3He/4He ratios with increasing distance to the SAF.