This study was designed to compare the efficacy and safety of seaprose S and serratio-peptidase in the treatment of venous inflammatory disease. Forty patients entered the study (11 males, 29 females), mean age 54.3 years (range 30-77), mean weight 74.8 kg (range 51-96), with superficial thrombophlebitis. The trial was conducted following a controlled, between patients, randomized experimental design. Seaprose S was administered as 30 mg tablets at a daily dosage of 90 mg (one tab t.i.d.), and serratio-peptidase as 5 mg tablets, at a dose of 30 mg per day (two tabs t.i.d.), both orally, for 14 days. Twenty patients received seaprose S and 20 serratio-peptidase. The findings indicate that seaprose S was more effective and better tolerated than serratio-peptidase. Although the group of patients assigned to seaprose S had considerably more severe initial symptoms, by the end of treatment spontaneous pain was reduced 68.7% from the baseline mean score (from 3.2 to 1.0), as compared with a 63.3% reduction in the serratio-peptidase group (from 3.0 to 1.1). Pain on pressure was reduced 61.1% with seaprose S (from 3.6 to 1.4), compared to 57.6% with the reference treatment (from 3.3 to 1.4). Edema was reduced respectively 75% (from 1.6 to 0.4) and 56.2% (from 1.6 to 0.7); erythema diminished 72.4% (from 2.9 to 0.8) and 58.3% (from 2.4 to 1.0); nighttime cramps were 61.1% less (from 1.8 to 0.7) compared with 52.9% (from 1.7 to 0.8); hemorrhagic suffusion was 53.3% less (from 1.5 to 0.7) compared with 41.7% (from 1.2 to 0.7); cutaneous dystrophy was reduced by 11.1% (from 1.8 to 1.6) and 7.7% (from 1.3 to 1.2). At the end of the treatment with seaprose S efficacy was assessed as good or excellent in 85% of the cases, compared with 65% for serratio-peptidase. Seaprose S caused no adverse reactions. During serratio-peptidase treatment one patient reported diarrhea, requiring temporary dosage reduction and specific treatment. It can thus be confirmed that seaprose S was effective and well tolerated in patients with inflammatory venous diseases.