We examined hyperactivation and acrosomal loss in asthenozoospermic patients with a history of failed in-vitro fertilization (IVF). After selection by a Percoll gradient, spermatozoa were incubated with 3.6 mM pentoxifylline (PTX), 3.0 mM 2-deoxyadenosine (2-DXA) or both. Hyperactivation and ionophore A-23187-induced acrosome reaction were assessed immediately after sperm treatment and again after 180 min. In all groups studied, the mean hyperactivation rates were found to be low. No significant differences were noted between assessments immediately after treatment and 180 min later, except after treatment with both PTX and 2-DXA. The mean hyperactivation rates were found not to improve as a result of either PTX or 2-DXA, while the combination of both PTX and 2-DXA revealed a significant enhancement of total hyperactivation. When individual hyperactivation rates between control and treated sperm samples were compared, large differences in response were observed. Some sperm samples showed a marked increase in hyperactivation with one treatment, while another treatment led to a decrease. Acrosome reaction rates assessed immediately after ionophore A-23187 stimulation were found not to be significantly different from those assessed 180 min later. No significant effect could be demonstrated for either treatment, although, here too, marked interindividual variations were noted. It was concluded that an unselective use of PTX, 2-DXA or both compounds together, may restore sperm function in certain of these patients, and perhaps improve fertilization in vitro, but in others it may produce no change or may even be detrimental to sperm function.