Presenting characteristics, long-term outcome, and techniques used in the diagnosis of 143 infants with suspected biliary obstruction are reviewed. Sixty-nine patients had surgically confirmed extrahepatic disease and 74 had intrahepatic disorders. A disproportionate number of infants with intrahepatic disease were boys (p = 0.013), low birthweight (p = 0.001), or had siblings with liver disease (p = 0.017). An initial total bilirubin of 20 mg/dl or greater was rare except in the intrahepatic disease category of neonatal hepatitis of known cause (p = 0.006). The initial percutaneous liver biopsy correctly predicted the ultimate diagnosis in 94 percent of all 143 patients. A methodological outline to diagnosis is presented, emphasizing early recognition of symptoms and careful follow-up with hepatobiliary imaging, liver biopsy, and surgical exploration, if required, until definitive diagnosis is made. This approach has aided us in reducing the age of diagnosis of biliary atresia from 12.8 +/- SD 7.3 weeks during the period 1971 through 1979 to 6.8 +/- SD 2.6 weeks from 1980 to 1982 (p = 0.0015). Eighteen-month survival has improved from 25 to 60 percent.