From May 1983 to June 1986, 40 patients with primary liver cancer, less than 5 cm in diameter, were treated by operation. The smallest lesion was 1.4 x 0.9 x 0.4 cm in size. Fifteen patients came to the hospital for treatment due to the finding of AFP greater than or equal to 31 ng/ml by public survey and 8 with space occupying lesion (SOL) in the liver by ultrasonography (US). The serum AFP levels ranged from 0 to 6800 ng/ml in this group with AFP negative in 6 cases, 31-400 ng/ml in 19 and over 400 ng/ml in 15. The positive rate of AFP was 37.5%. US displayed SOL in 25 cases, suspicious SOL in 5 and negative in 10. The positive rate was 62.5% by US. The overall positive rate was 77.5% by AFP and US combined. In addition, AFP variant was determined by LCA affino-crossed-immunoelectrophoresis autoradiography. LCA-nonreactive-AFP varied from 0 to 100% with a mean value of 57.0 +/- 26.7%. Taking less than 75% as diagnostic criterion for liver cancer, the positive rate of LCA-nonreactive-AFP was 65.0%. 12 patients who were AFP variant positive but SOL suspicious or negative were regularly followed by US for 1-20 months. They all showed distinct SOL. Composite results of AFP, AFP variant and US gave a diagnostic rate of 97.5% for small liver cancer. The determination of AFP variant is helpful in early detection of small liver cancer.