Two situations that result in the conversion of human mid-cycle cervical mucus from a sperm-receptive to a sperm-hostile form are described here: firstly, the addition of mucospissic agents, and secondly, the presence of antisperm antibodies. Two mucospissic biguanides were studied, chlorhexidine and Vantocil; both were totally spermicidal in the range 1-10 mg ml-1. Treatment of mucus with 1.5 microM to 1.65 mM Vantocil caused a dose-dependent increase in the dynamic storage modulus. The compatibility of the two biguanides with mucus was examined by measuring the rate of entry of diffusion of the [14C]biguanides into mucus. Chlorhexidine entered the mucus up to 0.53 mM, i.e. the highest concentration used, whilst Vantocil only entered at concentrations below 0.53 mM. This limited entry may be caused by the precipitation of mucus at the interface, producing a barrier of reduced permeability. The behaviour of purified mucin on ultracentrifugation was also altered after treatment with chlorhexidine. The s20 (at 2 mg ml-1 purified mucin) increased from 11.2 S to 19.3 S upon addition of 200 microM chlorhexidine. Further indication of structural alteration of biguanide-treated mucin was given by its loss of solubility in 0.22 M-sodium thiocyanate. The application of these biguanides to vaginal contraception is suggested. When antisperm antibodies are present in either the semen or cervical mucus, we suggest that an interaction can occur between galactose residues on the spermatozoa and galactose recognition sites on the antisperm antibody; in addition, binding can also occur between the Fc region of the antibody and cervical mucus. This process could therefore contribute to the binding of spermatozoa to the antibody and the immobilisation of this complex by the cervical mucus that is seen in immunological infertility. It was shown, by Immunobead binding, that immediate exposure of spermatozoa to D-galactose in the presence of chymotrypsin resulted in a considerable decrease or total loss of bound antisperm antibodies in males who had previously had a high titre of antibody. This reduction in the antibody level on the spermatozoa was accompanied by the appearance of the antibody level on the spermatozoa was accompanied by the appearance of the ability of the spermatozoa to penetrate cervical mucus in those couples examined. This pretreatment regimen for the ejaculate is suggested as a form of therapy for infertility related to the presence of antisperm antibodies.