Information on the structures of the oligosaccharides linked to Asn residues 159 and 391 of the human complement protease C1s was obtained using mass spectrometric and monosaccharide analyses. Asn 1 5 9 is linked to a complex-type biantennary, bisialylated oligosaccharide NeuAc2 Gal2 GlcNAc4 Man3 (molecular mass = 2206 ± 1). Asn 3 9 1 is occupied by either a biantennary, bisialylated oligosaccharide, or a triantennary, trisialylated species NeuAc3 Gal3 GlcNAc5 Man3 (molecular mass = 2861 ± 1), or a fucosylated triantennary, trisialylated species NeuAc3 Gal3 GlcNAc5 Man3 Fuc1 (molecular mass = 3007 ± 1), in relative proportions of approximately 1:1:1. The carbohydrate heterogeneity at Asn 3 9 1 gives rise to three major types of C1s molecules of molecular masses 79,318 ± 8(A), 79,971 ± 8(B), and 80,131 ± 8(C), with an average mass of 79,807 ± 8. A minor modification, yielding an extra mass of 132 ± 2, is also detected within positions 1-153.