Fetal grafts containing the hypothalamic suprachiasmatic nucleus (SCN), the site of an endogenous circadian pacemaker, can reinstate behavioral rhythms in lesioned recipients but the precise routes of communication between the graft and the host brain remain unknown. Grafts containing the SCN may convey temporal information to the host brain via neural efferents, diffusible factors, or a combination of both. We examined graft-host connections in anterior hypothalamic homografts (hamster-to hamster) and heterografts (rat-to hamster) implanted in the third ventricle by: (a) applying the carbocyanine dye, diI, directly onto homo- and heterografts in fixed tissue sections; and (b) using a donor-specific neurofilament (NF) antibody to immunocytochemically visualize heterograft efferents. DiI applied onto either homografts or heterografts labeled relatively few graft efferents which could be followed only short distances into the host brain. In contrast, NF-labeled heterograft efferents were both more numerous and extended for longer distances into the host brain than anticipated on the basis of diI tract tracing. The results suggest that anterior hypothalamic grafts implanted in the third ventricle provide substantial input to the adjacent host hypothalamus although it is not known whether these projections arise from SCN cells or from other extra-SCN hypothalamic tissue within these grafts. Nor is it known whether these projections are functional. To determine if neural efferents are required for the restoration of rhythmicity after grafting, we have encapsulated fetal anterior hypothalamus in a permselective polymer which prevents neurite outgrowth but allows diffusible signals to reach the host brain.(ABSTRACT TRUNCATED AT 250 WORDS)