Visual search and attentional alignment in 3D space are potentially modulated by information in unattended depth planes. The number of relevant and irrelevant items as well as their spatial relations may be regarded as factors which contribute to such effects. On a behavioral level, it might be different whether multiple distractors are presented in front of or behind target items. However, several studies revealed that attention cannot be restricted to a single depth plane. To further investigate this issue, two experiments were conducted. In the first experiment, participants searched for (multiple) targets in one depth plane, while non-target items (distractors) were simultaneously presented in this or another depth plane. In the second experiment, an additional spatial cue was presented with different validities to highlight the target position. Search durations were generally shorter when the search array contained two additional targets and were markedly longer when three distractors were displayed. The latter effect was most pronounced when a single target and three distractors coincided in the same depth plane and this effect persisted even when the target position was validly cued. The study reveals that the depth relation of target and distractor stimuli was more important than the absolute distance between these objects. Furthermore, the present findings suggest that within an attended depth plane, irrelevant information elicits strong interference. In sum, this study provides further evidence that allocation of attention is a flexible process which may be modulated by a variety of perceptual and cognitive factors.