We investigate the effective connectivity in the lateral geniculate nucleus and visual cortex of humans with amblyopia. Six amblyopes participated in this study. Standard retinotopic mapping stimuli were used to define the boundaries of early visual cortical areas. We obtained fMRI time series from thalamic, striate and extrastriate cortical regions for the connectivity study. Thalamo-striate and striate-extrastriate networks were constructed based on known anatomical connections and the effective connectivities of these networks were assessed by means of a nonlinear system identification method. The effective connectivity of all networks studied was reduced when driven by the amblyopic eye, suggesting contrary to the current single-cell model of localized signal reduction, that a significant part of the amblyopic deficit is due to anomalous interactions between cells in disparate brain regions. The effective connectivity loss was unrelated to the fMRI loss but correlated with the degree of amblyopia (ipsilateral LGN to V1 connection), suggesting that it may be a more relevant measure. Feedforward and feedback connectivities were similarly affected. A hemispheric dependence was found for the thalamo-striate feedforward input that was not present for the feedback connection, suggesting that the reduced function of the LGN recently found in amblyopic humans may not be solely determined by the feedback influence from the cortex. Both ventral and dorsal connectivities were reduced.