A challenge in photodynamic therapy (PDT) is to improve the tumour selectivity of the photosensitizers by using monoclonal antibodies (MAbs). With this aim, we developed MAb-conjugates with the hydrophobic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) and with the hydrophilic sensitizer aluminium (III) phthalocyanine tetrasulfonate (AI-PCS4). The capacity of these photoimmunoconjugates for selective targeting of squamous cell carcinoma (SCC) in vivo was demonstrated previously in SCC-bearing nude mice. Preliminary in vitro PDT studies with the vulvar SCC cell line A431 showed promising phototoxicity with both sensitizers when coupled to the internalizing MAb 42S. To rank the photosensitizers for their potential in photoimmunotherapy, we herein describe an extensive in vitro evaluation of mTHPC-MAb and AIPcS4-MAb conjugates. Both classes of conjugates were directly compared using 5 different SCC cell lines as target and 3 different MAbs (BIWA 4, E48 and 425) for tumour cell targeting. In contrast to free AIPcS4 (IC50 ≥ 700 nM), MAb-conjugated AIPcS4 was found to be highly phototoxic in PDT in all 5 cell lines. AIPcS4-BIWA 4 was most consistently effective with IC50 values ranging from 0.06-5.4 nM. mTHPC-MAb conjugates were in general hardly effective. Phototoxicity (log IC50) of the AIPcS4-MAb conjugates was found to be strongly correlated with their total cell binding capacity (internalized and surface bound) and to be less correlated with their internalization capacity. In conclusion, these data show a high potential of AIPcS4-MAb conjugates in comparison to mTHPC-MAb conjugates for use in PDT.