The effects of linker chain modifications were investigated in a series of cosalane analogues. The modifications investigated included: (1) shortening the three-carbon linker chain between the dichlorodisalicylmethane and the cholestane moiety by one carbon atom; (2) lengthening the linker chain by one carbon; (3) hydrogenation of the double bond in the linker chain; (4) changing the point of attachment of the linker chain from C-3 to C-6; (5) insertion of a phosphate between the steroid and the linker chain. With the exception of the phosphate modification, which abolished anti-HIV activity and increased cytotoxicity, the linker chain modifications produced relatively minor changes in anti-HIV activity and increased cytotoxicity, the linker chain modifications produced relatively minor changes in anti-HIV potency. The steroid and attached linker chain of cosalane therefore appear only to provide a general lipophilic appendage for the dichlorodisalicylmethane pharmacophore.