An aqueous water extract of Flos magnoliae, a Japanese Sino-medicine, inhibits angiogenesis in adjuvant-induced mouse pouch granuloma. Magnosalin (MSA) and magnoshinin(MSI), neolignans isolated from magnolia, have a crucial role in the anti-angiogenic effect of magnolia (Kimura et al., Int. Arch. Allergy Appl. Immunol., 93, 365 (1990); Phytother. Res., 6, 209 (1992)). We investigated the effects of these neolignans on tube formation of endothelial cells (EC) cultured in type I collagen gel during the angiogenic process. MSA (0.1-10 μM), MSI (0.23-7 μM) and corticosterone (CS : 0.3-30 μM) inhibited fetal bovine serum (FBS)-stimulated tube formation in a concentration-dependent manner. Their 30% inhibitory concentration (IC₃₀, 95% confidence limits) values were 0.51 (0.20-1.27) for MSA, 8.14 (2.48-26.7) for MSI and 3.65 μM (2.47-5.40) for CS, respectively. MSA and MSI (1-3 μM) also inhibited interleukin (IL)-1α-stimulated tube formation in a concentration-dependent manner. Their IC₅₀ values (95% confidence limits) were 1.22 (1.01-1.47) for MSA and 0.74 μM (0.24-2.31) for MSI against a submaximal concentration (69 pM) of IL-1α-stimulated tube formation. Their inhibitory effects on the action of IL-1α were non-competitive. These results demonstrate that MSA inhibited FBS-stimulated tube formation with a greater potency than MSI. The inhibitory effect of MSA on the action of FBS differed from that on the action of IL-1α.