Background Excessive alcohol use can cause macrostructural tissue shrinkage with regional preference for frontal systems. The extent and locus of alcoholism's effect on white matter microstructure is less known. Methods Quantitative fiber tracking derived from diffusion tensor imaging (DTI) assessed the integrity of samples of 11 major white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy control subjects (42 men, 46 women). Fiber integrity was expressed as fractional anisotropy (FA) and apparent diffusion coefficient (ADC), quantified separately for longitudinal diffusivity (λL), a putative index of axonal integrity, and transverse diffusivity (λT), a putative index of myelin integrity. Results Alcoholism affected FA and diffusivity, particularly λT, of several fiber bundles. Frontal and superior sites (frontal forceps, internal and external capsules, fornix, and superior cingulate and longitudinal fasciculi) showed greatest abnormalities in alcoholics relative to control subjects. More posterior and inferior bundles were relatively spared. Lifetime alcohol consumption correlated with regional DTI measures in alcoholic men but not women. When matched for alcohol exposure, alcoholic women showed more DTI signs of white matter degradation than alcoholic men in several fiber bundles. Among all alcoholics, poorer performance on speeded tests correlated with DTI signs of regional white matter degradation. Conclusions This survey of multiple brain fiber systems revealed a differential pattern of alcoholism's effect on regional FA and diffusivity with functional consequences attributable in part to compromised fiber microstructure with prominence in signs of myelin degradation. Sex-based differences suggest that women are at enhanced risk for alcoholism-related degradation in selective white matter systems.